PURPOSE: B-cell survival and differentiation critically depend on the interaction of BAFF-R and TACI with their ligands, BAFF and APRIL. Mature B-cell defects lead to Common Variable Immunodeficiency (CVID), which is associated with elevated serum levels of BAFF and APRIL. Nevertheless, BAFF-R and TACI expression in CVID and their relationship with ligand availability remain poorly understood. METHODS AND RESULTS: We found that BAFF-R expression was dramatically reduced on B cells of CVID patients, relative to controls. BAFF-R levels inversely correlated with serum BAFF concentration both in CVID and healthy subjects. We also found that recombinant BAFF stimulation reduced BAFF-R expression on B cells without decreasing transcript levels. On the other hand, CVID subjects had increased TACI expression on B cells in direct association with serum BAFF but not APRIL levels. Moreover, splenomegaly was associated with higher TACI expression, suggesting that perturbations of TACI function may underlie lymphoproliferation in CVID. CONCLUSIONS: Our results indicate that availability of BAFF determines BAFF-R and TACI expression on B cells, and that BAFF-R expression is controlled by BAFF binding. Identification of the factors governing BAFF-R and TACI is crucial to understanding CVID pathogenesis, and B-cell biology in general, as well as to explore their potential as therapeutic targets.
PURPOSE: B-cell survival and differentiation critically depend on the interaction of BAFF-R and TACI with their ligands, BAFF and APRIL. Mature B-cell defects lead to Common Variable Immunodeficiency (CVID), which is associated with elevated serum levels of BAFF and APRIL. Nevertheless, BAFF-R and TACI expression in CVID and their relationship with ligand availability remain poorly understood. METHODS AND RESULTS: We found that BAFF-R expression was dramatically reduced on B cells of CVIDpatients, relative to controls. BAFF-R levels inversely correlated with serum BAFF concentration both in CVID and healthy subjects. We also found that recombinant BAFF stimulation reduced BAFF-R expression on B cells without decreasing transcript levels. On the other hand, CVID subjects had increased TACI expression on B cells in direct association with serum BAFF but not APRIL levels. Moreover, splenomegaly was associated with higher TACI expression, suggesting that perturbations of TACI function may underlie lymphoproliferation in CVID. CONCLUSIONS: Our results indicate that availability of BAFF determines BAFF-R and TACI expression on B cells, and that BAFF-R expression is controlled by BAFF binding. Identification of the factors governing BAFF-R and TACI is crucial to understanding CVID pathogenesis, and B-cell biology in general, as well as to explore their potential as therapeutic targets.
Authors: J S Thompson; S A Bixler; F Qian; K Vora; M L Scott; T G Cachero; C Hession; P Schneider; I D Sizing; C Mullen; K Strauch; M Zafari; C D Benjamin; J Tschopp; J L Browning; C Ambrose Journal: Science Date: 2001-08-16 Impact factor: 47.728
Authors: L D Zhao; Y Li; M F Smith; J S Wang; W Zhang; F L Tang; X P Tian; H Y Wang; F C Zhang; D N Ba; W He; X Zhang Journal: Lupus Date: 2010-11 Impact factor: 2.911
Authors: M Fabris; L Quartuccio; S Sacco; G De Marchi; G Pozzato; C Mazzaro; G Ferraccioli; T S Migone; S De Vita Journal: Rheumatology (Oxford) Date: 2006-05-30 Impact factor: 7.580
Authors: J A Gross; J Johnston; S Mudri; R Enselman; S R Dillon; K Madden; W Xu; J Parrish-Novak; D Foster; C Lofton-Day; M Moore; A Littau; A Grossman; H Haugen; K Foley; H Blumberg; K Harrison; W Kindsvogel; C H Clegg Journal: Nature Date: 2000-04-27 Impact factor: 49.962
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Authors: T Koyama; H Tsukamoto; Y Miyagi; D Himeji; J Otsuka; H Miyagawa; M Harada; T Horiuchi Journal: Ann Rheum Dis Date: 2004-12-02 Impact factor: 19.103
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Authors: P Schneider; F MacKay; V Steiner; K Hofmann; J L Bodmer; N Holler; C Ambrose; P Lawton; S Bixler; H Acha-Orbea; D Valmori; P Romero; C Werner-Favre; R H Zubler; J L Browning; J Tschopp Journal: J Exp Med Date: 1999-06-07 Impact factor: 14.307
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